Incontinentia pigmenti in a newborn with a novel nonsense mutation in the NEMO gene.
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Codon, Nonsense↗
Biomedical subjects
A Volz
Publications and source records attributed to A Volz.
Mastix, a known herbal allergen, as causative agent in occupation-related dermatitis.
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Adhesives↗
The soluble pool of HLA-G produced by human trophoblasts does not include detectable levels of the intron 4-containing HLA-G5 and HLA-G6 isoforms.
In the context of implantation and pregnancy, several immunomodulating functions have been attributed to the different HLA-G isoforms. Increasing attention is now being addressed to the actively secreted soluble forms, because they might have a systemic function or could be useful as diagnostic tools. However, the cellular source of secretion, even during pregnancy, where HLA-G expression level is known to be highest, is still under debate. To elucidate the conflicting results, we investigated the isoform distribution in human first trimester and term placentas in situ and in vitro. Results obtained by applying immunohistochemistry, western blot, enzyme-linked immunosorbent assay (ELISA) and RT-PCR show that (1) all of the alpha1 domain-containing HLA-G isoforms are restrictedly expressed in the extravillous cytotrophoblasts (EVCTs) and very few first-trimester syncytiotrophoblasts, which directly cover cell columns, whereas mesenchymal cells of the villous chorion do not express HLA-G; (2) as demonstrated in western blots, trophoblasts express only the HLA-G1 isoform; (3) HLA-G5 and -G6 transcripts could be detected in human term placenta and isolated first-trimester trophoblasts but levels are extremely low; and (4) conditioned media of primary first-trimester trophoblasts, and the chorion laeve-derived trophoblastic cell line AC1-M59 do contain HLA-G1 fragments shed from the cell surface. Our data provide substantial evidence that none of the intron 4-containing isoforms, the so-called actively secreted, soluble HLA-G5 or -G6, are produced by human trophoblasts in situ or in vitro.
Alternative Splicing↗
Soluble HLA-G, the discussion is going on!
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Alternative Splicing↗
[Polytrauma with tension pneumothorax with inserted chest tube].
The authors report a case of a 25-year-old woman with a polytrauma, caused by a free fall of 12 metres in suicidal intention. Following endotracheal intubation and mechanical ventilation by an emergency physician at the scene, the patient was delivered to the emergency room of an university hospital. An ultrasonic check of the abdomen revealed free fluid in the abdominal cavity, and a rupture of liver and spleen was suspected. Since breath sounds over the right lung were diminished, a chest tube was inserted immediately in the fifth intercostal space in the anterior axillary line. About 300 millilitres of blood were drained by the tube. Shortly thereafter, a laparotomy was performed, where spleen and liver rupture were confirmed and treated. After 60 minutes, the patient developed severe hypotension coupled with ventricular tachycardia and fibrillation, and resuscitation measures had to be initiated. Since breath sounds over the right lung were missing, a tension pneumothorax was suspected and a thoracotomy performed immediately. While huge amounts of air and blood were emerging from the thoracic cavity, a rupture of the right mainstem bronchus as well as of the right pulmonary artery and vena subclavia was identified. The chest tube was found dislocated into the subcutaneous tissue. Despite of open heart compression, application of adrenaline and noradrenaline and substitution of packed red blood cells and of crystalloid and colloid solutions, all resuscitation measures failed so that the patient died shortly after on the operation table. This case illustrates first the difficulties of an adequate thoracic trauma management, particularly, when clinical symptoms are discrete, second the problems of the insertion and control of a chest tube, and third risks associated with wrong position or secondary dislocation which may include - as in our case - "masking" of severe injury patterns and delay of life-saving measures such as an immediate thoracotomy. In order to improve prognosis of patients with poly-/thoracic trauma, establishment of spiral-CT in emergency centres, routine bronchoscopy and safe handling of chest tubes may be helpful.
Adult↗
Delays to treatment and out-of-pocket medical expenditure for tuberculosis patients, in an urban area of South America.
Short delays to treatment are important for the control of tuberculosis (TB). National Tuberculosis Programmes provide free diagnosis and treatment for smear-positive patients, so that the patients' out-of-pocket medical expenditure could be almost nil. The factors associated with delays in starting treatment, and the pre-treatment out-of-pocket medical expenditure for TB patients, have now been investigated in the Bolivian city of Cochabamba. Bolivia is the Latin American country with the highest incidence of TB. It is covered by a national TB programme that provides free diagnosis and free treatment for smear-positive patients. Structured interviews with 144 smear-positive patients enrolled in this programme revealed median patient, provider and total delays of 3.6, 6.2 and 12.9 weeks, respectively. The total delays were longer for the female patients than for the male, and for patients who consulted private doctors than for the other patients. When the first healthcare provider was a doctor, the median provider delay was 4.9 weeks in the public sector but 7.2 weeks in the private. The median out-of-pocket medical expenditure per patient, which was U.S.$13.2 overall, was much higher for those who consulted a private doctor than for those who did not (U.S.$21.9 v. U.S.$5.4, respectively; P<0.001). It appears that interventions targeting doctors (in both the private and public sectors) are likely to have a larger impact on the shortening of delays in TB treatment than interventions targeting patients. They could also reduce unnecessary out-of-pocket expenditure.
Adolescent↗
Tuberculosis control and the private health sector in Bolivia: a survey of pharmacies.
BACKGROUND: Bolivia is a high tuberculosis (TB) incidence country with a large private for-profit health sector. TB drug sales in private pharmacies are not illegal. OBJECTIVES: To measure the availability of TB drugs in private pharmacies, study vendors' attitudes, and explore the potential for collaboration between the public health sector and pharmacies. METHODS: Simulated clients visited a random sample of 100 pharmacies in the city of Cochabamba, presenting with a prescription for four TB drugs. After the survey, contacts were made with the local Pharmacist's Association. RESULTS: Twenty-five pharmacies sold at least one drug, 23 sold rifampicin and 16 sold isoniazid. Of 99 pharmacies unable to fill the whole prescription, 59 referred the client to another pharmacy, and 22 to the public services. Pharmacists said that rifampicin was often prescribed for non-TB indications, and that TB drug sales were of minimal contribution to their income. They agreed to stop selling the drugs and to refer clients seeking them to the public sector. CONCLUSION: This study has documented a small market for TB drugs sales in private pharmacies and provided the opportunity to start collaboration with the pharmacists. Our results suggest that the private sector contributes little to managing TB in Bolivia.
Antitubercular Agents↗
Nucleation and growth of molecular organic crystals in a liquid film under vapor deposition.
We report on the nucleation and growth of tetracene in a thin liquid film which is continuously supersaturated by vapor deposition of molecules onto the film. In a first stage, nucleation and fast anisotropic two-dimensional dendritic growth occurs. In a second stage, the dendrites coarsen into pallet-shaped crystals. These are highly oriented with respect to the plane of the liquid film and reach a lateral size of several 100 microm. The two-dimensional growth mode is explained by the confined growth geometry in the liquid in combination with the anisotropy of the crystal structure.
Journal Article↗
Genotype-phenotype correlations in PCD patients carrying DNAH5 mutations.
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Genotype↗
Candidate gene analysis of KIAA0678 encoding a DnaJ-like protein for adolescent nephronophthisis and Senior-Løken syndrome type 3.
Nephronophthisis (NPH), an autosomal recessive cystic kidney disease, causes progressive renal failure. The gene for adolescent nephronophthisis (NPHP3) has been mapped to chromosome 3q21-->q22. Senior-Løken syndrome (SLS) describes the association of NPH and Leber congenital amaurosis. Recently a locus for Senior-Løken syndrome (SLSN3) has been localized on chromosome 3q21-->q22 containing the whole critical NPHP3 region. Within the critical NPHP3/SLSN3 region we identified the gene KIAA0678 encoding a DnaJ-like protein. KIAA0678 was considered a good functional candidate gene for NPH3 and SLS3, because molecular cha- perones are involved in the etiology of renal and retinal diseases. Analysis of the genomic structure of KIAA0678 identified 25 exons. For mutational analysis all exons and intron-exon boundaries were amplified and directly sequenced. Affected individuals of two NPH3 families and one SLS family with haplotypes indicative for homozygosity by descent for the NPHP3/SLSN3 locus were studied. No mutation in KIAA0678 was detected. We conclude, KIAA0678 most likely is not responsible for NPH and SLS in the patients studied.
Adolescent↗
[Methods of process analysis, instruments of quality management. Successful implementation of quality projects].
Meaningful experience and knowledge--the prerequisite for the successful implementation of quality projects--are described in terms of their practical importance on the basis of the experience gained with quality management in the municipal hospital at München-Schwabing (HMS). Against the background of the process of quality assurance or PDCA (Plan Do Check Act), the approach to the selection of suitable themes (problem selection), the prioritization of projects, the appropriate composition of the project group, the description of the problem, and the organization of the project, are discussed. The authors describe the implementation of methods of process analysis such as flow diagrams and cause-and-effect diagrams. The importance of evaluation is justified, and pragmatic approaches are presented. The importance of project documentation and essential contents are discussed.
Germany↗
A human mitochondrial ferritin encoded by an intronless gene.
Ferritin is a ubiquitous protein that plays a critical role in regulating intracellular iron homoeostasis by storing iron inside its multimeric shell. It also plays an important role in detoxifying potentially harmful free ferrous iron to the less soluble ferric iron by virtue of the ferroxidase activity of the H subunit. Although excess iron is stored primarily in cytoplasm, most of the metabolically active iron in cells is processed in mitochondria. Little is yet known of how these organelles regulate iron homeostasis and toxicity. Here we report an unusual intronless gene on chromosome 5q23.1 that encodes a 242-amino acid precursor of a ferritin H-like protein. This 30-kDa protein is targeted to mitochondria and processed to a 22-kDa subunit that assembles into typical ferritin shells and has ferroxidase activity. Immunohistochemical analysis showed that it accumulates in high amounts in iron-loaded mitochondria of erythroblasts of subjects with impaired heme synthesis. This new ferritin may play an important role in the regulation of mitochondrial iron homeostasis and heme synthesis.
Amino Acid Sequence↗
Genesis of the ILT/LIR/MIR clusters within the human leukocyte receptor complex.
The human leukocyte receptor complex (LRC) contains at least 26 genes which belong to the immunoglobulin superfamily The genes include two clusters of immunoglobulin-like transcript (ILT)/leukocyte immunoglobulin-like receptor (LIR)/monocyte-macrophage inhibitory receptor (MIR) loci, a cluster of killer cell inhibitory receptor (KIR) genes, two leukocyte-associated immunoglobulin-like receptor genes, as well as the Fc receptor for IgA and the natural cytotoxicity receptor I loci. It has already been postulated that these genes have evolved by multiple duplications, while the two ILT clusters are likely to have been generated by the inverse duplication of an ancient ILT cluster. To shed more light on the possible origin of the loci within the LRC, we have now investigated the presence of KIR and ILT loci in a variety of vertebrates by hybridizations and compared the genomic sequences of all ILT genes. Our results lead to the following conclusions: 1) the origin of KIR genes dates back to about 100 million years, but only primate and human KIRs are closely related; 2) in contrast, genes which are detectable with human ILT cDNAs are already found in birds, suggesting their presence already about 300 million years ago. Using the sequence data produced by the human genome project, we have developed a hypothesis that reconstructs the genesis of the two human ILT clusters in detail which will help to understand the function of the LRC.
Animals↗
Characterization of clustered MHC-linked olfactory receptor genes in human and mouse.
Olfactory receptor (OR) loci frequently cluster and are present on most human chromosomes. They are members of the seven transmembrane receptor (7-TM) superfamily and, as such, are part of one of the largest mammalian multigene families, with an estimated copy number of up to 1000 ORs per haploid genome. As their name implies, ORs are known to be involved in the perception of odors and possibly also in other, nonolfaction-related, functions. Here, we report the characterization of ORs that are part of the MHC-linked OR clusters in human and mouse (partial sequence only). These clusters are of particular interest because of their possible involvement in olfaction-driven mate selection. In total, we describe 50 novel OR loci (36 human, 14 murine), making the human MHC-linked cluster the largest sequenced OR cluster in any organism so far. Comparative and phylogenetic analyses confirm the cluster to be MHC-linked but divergent in both species and allow the identification of at least one ortholog that will be useful for future regulatory and functional studies. Quantitative feature analysis shows clear evidence of duplications of blocks of OR genes and reveals the entire cluster to have a genomic environment that is very different from its neighboring regions. Based on in silico transcript analysis, we also present evidence of extensive long-distance splicing in the 5'-untranslated regions and, for the first time, of alternative splicing within the single coding exon of ORs. Taken together with our previous finding that ORs are also polymorphic, the presented data indicate that the expression, function, and evolution of these interesting genes might be more complex than previously thought.
Amino Acid Sequence↗
Transcription factor GATA-2 gene is located near 3q21 breakpoints in myeloid leukemia.
Rearrangements affecting chromosome band 3q21 are observed in a subgroup of patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). However, little is known about the molecular consequences of such aberrations. We therefore established a PAC contig in the 3q21 breakpoint region and identified potential protein coding sequences by exon trapping. One of the exons isolated was from the human GATA-2 gene, which we showed to be transcribed from telomere to centromere. The majority of 3q21 breakpoints are located telomeric to the transcribed portion of this gene in a region that in mice appears to be necessary for proper promoter function. Results of GATA-2 expression analyses in leukemic cell lines as well as primary patient samples are compatible with the hypothesis that 3q21 aberrations contribute to leukemogenesis through deregulation of the hematopoietic transcription factor GATA-2.
Acute Disease↗
Extensive gene duplications and a large inversion characterize the human leukocyte receptor cluster.
The chromosomal region 19q13.4 harbors the human leukocyte receptor cluster (LRC) which has been demonstrated to contain 19 genes encoding leukocyte-expressed receptors of the immunoglobulin (Ig) superfamily. A spotted PAC library was used to construct a contig of 65 overlapping clones spanning the complete LRC. Within the 900 kb covered by the contig, we identified one cluster containing killer cell inhibitory receptor genes and two clusters containing Ig-like transcript (ILT) genes. Of these, the second ILT cluster, located at the centromeric end of the LRC, was previously unknown. Detailed analysis of the ILT receptor genes in this cluster revealed one novel (ILT11) and six already known ILT genes. The two ILT clusters are transcribed in opposite directions and are separated by about 200 kb, which contains two leukocyte-associated inhibitory receptor (LAIR) genes. The data suggest that the two ILT clusters, each including one LAIR locus, arose from a single ancestral ILT/LAIR cluster by inverse duplication of a c large genomic fragment. Furthermore, the NK cell-expressed NKp46 gene was localized 20 kb telomeric of FCAR; and 14 novel genes mapping within the LRC were identified by cDNA selection. Together with the gene for the ribosomal protein S9 (RPS9), which had previously been assigned to 19q13.4, the total number of LRC genes is now 44. Of these, 29 belong to the Ig superfamily.
Animals↗
Polymorphisms in olfactory receptor genes: a cautionary note.
The hundreds of human olfactory receptor (OR) genes are organized into clusters occurring on nearly every chromosome. Although their sequences are not always closely related, they share stretches of considerable similarity, both at the amino acid and nucleotide levels. We demonstrate here that an HLA complex-linked OR sequence, FAT11, for which recently a number of alleles have been claimed within the Hutterites, contains sequences derived from two closely related, linked OR genes, hs6M1-12 and hs6M1-16. Instead of indicating a difference between alleles of a given locus, two of the polymorphisms described for FAT11 (at amino acids 48 and 220 of the deduced protein sequence, respectively) may in fact reflect distinct sequences of hs6M1-12 and a further, closely related HLA-linked OR locus, hs6M1-13P. As a consequence, recombination rates in Hutterites in the region telomeric of HLA-G may have to be reconsidered.
Amino Acid Substitution↗
Identification, tissue specific expression, and chromosomal localisation of several human dynein heavy chain genes.
Sliding between adjacent microtubules within the axonema gives rise to the motility of cilia and flagella. The driving force is produced by dynein complexes which are mainly composed of the axonemal dynein heavy chains. We used cells of human respiratory epithelium after in vitro ciliogenesis to clone cDNA fragments of nine dynein heavy chain genes, one of which had never been identified before. Dynein heavy chains are highly conserved from protozoa to human and the evolutionary ancestry of these dynein heavy chain cDNA fragments was deduced by phylogenetic analysis. These dynein heavy chain cDNAs are highly transcribed in human tissues containing axonema such as trachea, testis and brain, but not in adult heart or placenta. PAC clones containing dynein heavy chains were obtained and used to determine by FISH their chromosomal position in the human genome. They were mapped to 2p12-p11, 2q33, 3p21.2-p21.1, 13q14, 16p12 and 17p12. The chromosomal assignment of these dynein heavy chain genes which was confirmed by GeneBridge 4 radiation hybrid screening, will be extremely useful for linkage analysis efforts in patients with primary ciliary dyskinesia (PCD).
Amino Acid Sequence↗